Ovarian hormone status and abdominal visceral adipose tissue metabolism

We examined abdominal sc and visceral adipose tissue metabolism in a sample of 19 regularly cycling premenopausal women (age 46.3 +/- 3.7 yr) and 10 women with natural menopause or pharmacological ovarian suppression (age 51.1 +/- 9.2 yr). Subcutaneous and visceral (omental, epiploic) adipose tissue biopsies were obtained during abdominal hysterectomies. Body composition and adipose tissue distribution were measured before the surgery by dual x-ray absorptiometry and computed tomography, respectively. Ovarian hormone-deficient women tended to be older (P = 0.08) and were characterized by increased visceral adipose tissue area (P < 0.05). Subcutaneous adipocyte size, lipoprotein lipase (LPL) activity, and basal lipolysis were not significantly different between groups. On the other hand, omental fat cell size was significantly higher in ovarian hormone-deficient women, compared with premenopausal women (P < 0.05). The omental/sc LPL activity ratio and omental adipocyte basal lipolysis were also significantly higher in ovarian hormone-deficient women (P < 0.05 for both comparisons). Significant positive correlations were found between visceral adipose tissue area and omental LPL activity (r = 0.54, P < 0.003), omental adipocyte basal lipolysis (r = 0.66, P < 0.0001), and omental fat cell size (r = 0.81, P < 0.0001). In multivariate analyses, ovarian status was no longer a significant predictor of adipose cell metabolism variables after visceral adipose tissue area was entered into the model, with the exception of the omental/sc LPL activity ratio, which remained independently associated with ovarian status. In conclusion, although the size of the visceral adipose tissue compartment was an important determinant of adipocyte metabolism in this depot, the increased omental/sc LPL activity ratio in ovarian hormone-deficient women supports the notion of a predominant visceral fat storage in these women.     

Regional differences in adipose tissue metabolism in obese men

We examined omental and subcutaneous adipose tissue adipocyte size, and lipolysis and lipoprotein lipase (LPL) activity in a sample of 33 men aged 22.6 to 61.2 years and with a body mass index ranging from 24.6 to 79.1 kg/m2. We tested the hypothesis that lipolysis rates would be higher in the omental fat depot than in subcutaneous adipose tissue and that this difference would persist across the spectrum of abdominal adiposity values. Omental and subcutaneous adipose tissue samples were obtained during surgery. Adipocytes were isolated by collagenase digestion. Adipocyte size and LPL activity as well as basal, isoproterenol-, forskolin-, and dibutyryl cyclic adenosine monophosphate-stimulated lipolysis were measured. Although adipocytes from both fat compartments were larger in obese subjects, no difference was observed in the size of omental vs subcutaneous fat cells. Lipoprotein lipase activity, expressed as a function of cell number, was significantly higher in omental than in subcutaneous fat tissue (P<.005). Basal lipolysis and lipolytic responses to isoproterenol, forskolin, or dibutyryl cyclic adenosine monophosphate, expressed either as a function of cell number or as a fold response over basal levels, were not significantly different in omental vs subcutaneous fat cells. When stratifying the sample in tertiles of waist circumference, adipocyte diameter was similar in the omental and subcutaneous depots for all adiposity values. Omental adipocyte size reached a plateau in the 2 upper tertiles of waist circumference, that is, from a waist circumference of 125 cm and above. Lipoprotein lipase activity was significantly higher in omental cells in the middle tertile of waist circumference (P=.05), and no regional difference was noted in lipolysis values across waist circumference tertiles. In conclusion, in normal-weight to morbidly obese men, although adipocyte size and lipolysis tended to increase with higher waist circumference, no difference was observed between the omental and subcutaneous fat depot.     

Local androgen inactivation in abdominal visceral adipose tissue

We examined the expression and activity of two enzymes from the aldoketoreductase (AKR) family 1C, namely type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD-5, AKR1C3) and type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD-3, AKR1C2) in female sc and omental adipose tissue and in preadipocyte primary cultures. 17beta-HSD-5 preferentially synthesizes testosterone from the inactive adrenal precursor androstenedione, whereas 3alpha-HSD-3 inactivates dihydrotestosterone. mRNAs of both enzymes were detected in adipose tissue from the omental and sc compartments. Real-time PCR quantification indicated a 3-fold higher 3alpha-HSD-3 expression compared with 17beta-HSD-5, and the expression of both enzymes tended to be higher in the sc vs. the omental depot. Accordingly, dose-response and time-course experiments performed in preadipocyte primary cultures indicated that 3alpha-HSD activity was higher than 17beta-HSD activity (13-fold maximum velocity difference). We measured 3alpha-HSD activity in omental and sc adipose tissue samples of 32 women for whom body composition and body fat distribution were evaluated by dual-energy x-ray absorptiometry and CT, respectively. We found that androgen inactivation in omental adipose tissue through 3alpha-HSD activity was significantly higher in women with elevated vs. low visceral adipose tissue accumulation (1.7-fold difference; P < 0.05). Moreover, omental adipose tissue 3alpha-HSD activity was positively and significantly associated with CT-measured visceral adipose tissue (r = 0.43; P < 0.02) and omental adipocyte diameter (r = 0.42; P < 0.02). These results indicate that local androgen inactivation is a predominant reaction in female abdominal adipose tissue, with the greatest conversion rates observed in the presence of abdominal visceral obesity. Increased androgen inactivation in omental adipose tissue of abdominally obese women may impact locally on the regulation of adipocyte metabolism.     

Variations of fat tissue fraction in abnormal human bone marrow depend both on size and number of adipocytes: a stereologic study

Studies dealing with the number or size of individual adipose cells in abnormal human bone marrow are lacking. To ascertain whether variations in fat tissue fraction depend on the size of individual adipocytes or their number or both, a stereologic study of 30 human bone marrow specimens (10 with aplasia, 10 with hyperplasia, and 10 with dysplasia) was performed. A total of 23,435 adipocyte profiles were measured and two stereologic parameters were obtained in each specimen: mean diameter and number of cells per mm3 of bone marrow. The fat tissue fraction correlated positively with the size (r = .79; P less than .001) and the number/volume (r = .77; P less than .001) of adipocytes. The significance of both adipocyte size and adipocyte number/volume was confirmed by stepwise multiple regression, in which the size alone explained 62.5% of fat tissue fraction and both size and number/volume explained 95.8% of fat tissue fraction. These results are discussed from a pathophysiologic point of view.     

The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women

The recently discovered hormone leptin is primarily secreted by adipose tissue and serves as an internal signal indicating the size of body fat stores. The aim of the present study was to investigate the impact of the dietary fatty acid composition on serum leptin concentrations. Therefore, serum leptin levels were measured by RIA in healthy nonobese men (n = 30) and women (n = 25). First, all participants received a baseline high-fat diet, rich in saturated fat, for 2 wk and were then randomly assigned to one of three high-fat dietary treatments, which contained refined olive oil (rich in monounsaturated fatty acids, n = 19), rapeseed oil [rich in monounsaturated fatty acids and alpha-linolenic acid (18:3n-3), n = 17], or sunflower oil (rich in n-6-polyunsaturated fatty acids, n = 19) as the principal source of fat for 4 wk. On the rapeseed oil diet, serum leptin concentrations increased slightly in men [+0.25 ng/ml, T(9) = -2.778, P = 0.021], but decreased distinctly in women [-4.70 ng/ml, T(6) = 5.083, P = 0.002]. Both the olive oil and the sunflower oil diet did not affect serum leptin concentrations. Thus, it is proposed that serum leptin levels were affected by the high amount of alpha-linolenic acid in rapeseed oil. However, questions remain as to why this diet differently affected serum leptin in men and women.     

Adipose tissue levels of fatty acids and tocopherol in young and old women

Tocopherol concentration and fatty acid composition were determined in samples of subcutaneous adipose tissue from 33 young and 28 old women. Young women exhibited more saturated fatty acids and less monounsaturated fatty acids than old women (p less than 0.01). Adipose tissue tocopherol correlated with plasma tocopherol, with r = 0.49 and p less than 0.01, when the data for young and old were combined. A negative association was found between adipose tissue tocopherol and the n-3/n-6 fatty acid ratio in the old women (r = 0.42; p less than 0.05), suggesting that the tocopherol content of adipose tissue is determined not only by the intake of the nutrient but also by the tissue fatty acid composition.     

Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids

OBJECTIVE: Obesity is associated with reduced insulin sensitivity and extensive reorganization of adipose tissue. As polyunsaturated fatty acids (PUFA) appear to inhibit diabetes development, we investigated PUFA effects on markers of matrix remodeling in white adipose tissue. METHODS AND PROCEDURE: Male obese diabetic (db/db) mice were treated with either a low-fat standard diet (LF), or high-fat diets rich in saturated and monounsaturated fatty acids (HF/S), n-6 PUFA (HF/6) or the latter including marine n-3 PUFA (HF/3). White adipose tissue was analyzed for gene expression, fatty acid composition and by immunofluorescence. RESULTS: HF/S treatment increased adipose tissue expression of a number of genes involved in matrix degradation including matrix metalloproteinase (MMP)-12, -14 and cathepsin K, L and S compared with LF. MMP-12 gene was expressed in macrophages and adipocytes, and MMP-12 protein colocalized with both cell types. In addition, mean adipocyte area increased by 1.6-fold in HF/S-treated mice. Genes essential for collagen production, such as procollagen I, III, VI, tenascin C and biglycan were upregulated in HF/S-treated animals as well. N-3 PUFA supplementation resulted in enrichment of these fatty acids in adipose tissue. Moreover, n-3 PUFA inhibited the HF/S-induced upregulation of genes involved in matrix degradation and production I restored mean adipocyte area and prevented MMP-12 expression in macrophages and adipocytes. CONCLUSION: N-3 PUFA prevent high-fat diet-induced matrix remodeling and adipocyte enlargement in adipose tissue of obese diabetic mice. Such changes could contribute to diabetes prevention by n-3 PUFA in obese patients.     

Age-related variations of fat tissue fraction in normal human bone marrow depend both on size and number of adipocytes: a stereological study

Studies dealing with the number or size of individual adipose cells in human bone marrow are lacking. To ascertain whether the age-related variations in fat tissue fraction depend on the size of individual adipocytes or their number or both, a stereological study of 20 normal human bone marrow specimens was performed. A total number of 17,039 adipose cell profiles was measured and two stereological parameters were obtained in each specimen: mean diameter and number of cells per mm3 of bone marrow. With increasing age, an increasing fat tissue fraction was observed (r = 0.61; p = 0.004). The fat tissue fraction correlated positively with the size (r = 0.81; p less than 0.001) and the number/volume (r = 0.59; p = 0.006) of adipocytes. The significance of both adipocyte size and adipocyte number/volume was confirmed by stepwise multiple regression, in which the size alone explained 66.2% of fat tissue fraction and both size and number/volume explained 97.2% of fat tissue fraction. These results are discussed from a pathophysiological point of view.     

Effects of long-chain monounsaturated and n-3 fatty acids on fatty acid oxidation and lipid composition in rats

Long-chain n-3 fatty acids and fat fish are reported, among multiple physiological properties, to enhance peroxisomal beta-oxidation and effect triacylglycerol status. Long-chain n-3 and monounsaturated fatty acids are the main portion of fatty acids in fat fish. The individual effect of long-chain monounsaturated fatty acids on beta-oxidation and fatty acid composition was tested and compared to the effect of n-3 polyunsaturated and saturated fatty acids in a 3-week feeding experiment of rats. To explore the contribution from long-chain monounsaturated fatty acids in these aspects, the effect of long-chain n-3 and monounsaturated fatty acids on mitochondrial and peroxisomal beta-oxidation was compared, as well as fatty acid composition of adipose tissue, liver and serum. Fatty acid oxidase, palmitoyltransferase I and II activities, the amount of serum lipids, and the fatty acid composition of lipid fractions from the organs were analysed. The peroxisomal beta-oxidation was enhanced by the n-3 fatty acids, whereas a small, significant increase with the monounsaturated fatty acids was observed. There was a stimulation of the mitochondrial oxidation with the n-3 fatty acids, but monounsaturated fatty acids gave a small, nonsignificant decrease. With n-3 fatty acids there was a considerable decrease in the levels of serum triacylglycerol, phospholipids, free fatty acids and total cholesterol, while there were only minor effects of monounsaturated fatty acids. As judged from the fatty acid composition data, there was a mobilization on n-3 fatty acids from the adipose tissue to liver and plasma with the n-3 diet. This observation was also seen with the monounsaturated fatty acid-enriched diet. In conclusion, monounsaturated fatty acids seemed to stimulate peroxisomal beta-oxidation and to increase plasma triacylglycerol, whereas the mitochondrial oxidation was slightly decreased.     

The role of dietary fat in human obesity

Both the amount and quality of dietary fat have been implicated in the pathogenesis of obesity. Adipose tissue fatty and composition, which is known to reflect dietary intake, was sampled in 413 free-living, healthy American males appearing for a routine medical examination. The average age was 46.8 +/- 11.4 years (mean +/- s.d.) and body mass index (BMI)--weight/height--was 25.2 +/- 3.4. The BMI was correlated (P less than 0.01) with known risk factors for cardiovascular disease as follows: total cholesterol (TC) r = 0.18, triglycerides (TG) r = 0.32, low-density lipoprotein cholesterol (LDL-C) r = 0.18, high-density lipoprotein cholesterol (HDL-C) r = -0.24, systolic and diastolic blood pressure (BP) r = 0.30. Underlying patterns which might be related to diet were sought in the distribution of the seven major fatty acids in adipose tissue. Statistical analysis permitted delineation of three factors which were hypothetically related to animals fat intake (F1--monounsaturates), carbohydrate intake (F2--saturates) and vegetable oil intake (F3--polyunsaturates). F1 and F3 together accounted for 12 percent of the variance in BMI while F2 had no influence. Our conclusions are that the variance in BMI is related much more to non-dietary factors than to adipose tissue fatty acid composition and that the nature of dietary fat was not a major distinguishing factor in obesity in this population. There was also no evidence for a high dietary carbohydrate (low fat) intake in the obese.     

Fatty acid compositions of lipids in mesenteric adipose tissue and lymphoid cells in patients with and without Crohn's disease and their therapeutic implications

BACKGROUND: The physiological bases for roles of adipose tissue and fatty acids in the symptoms and dietary treatments of Crohn's disease (CD) are poorly understood. The hypothesis developed from experiments on rodents that perinodal adipocytes are specialized to provision adjacent lymphoid tissues was tested by comparing the composition of triacylglycerol and phospholipid fatty acids in homologous samples of mesenteric adipose tissue and lymph nodes from patients with or without CD. METHODS: Mesenteric perinodal and other adipose tissue and lymph nodes were collected during elective surgery for CD and other conditions. Fatty acids were extracted, identified, and quantified by thin-layer and gas-liquid chromatography. RESULTS: Perinodal adipose tissue contained more unsaturated fatty acids than other adipose tissue in controls, as reported for other mammals, but site-specific differences were absent in CD. Lipids from adipose and lymphoid tissues had more saturated fatty acids but fewer polyunsaturates in patients with CD than controls. In adipose tissue samples, depletion of n-3 polyunsaturates was greatest, but n-6 polyunsaturates, particularly arachidonic acid, were preferentially reduced in lymphoid cells. Ratios of n-6/n-3 polyunsaturates were higher in adipose tissue but lower in lymphoid cells in patients with CD than in controls. CONCLUSIONS: Site-specific differences in fatty acid composition in normal human mesentery are consistent with local interactions between lymph node lymphoid cells and adjacent adipose tissue. These site-specific properties are absent in CD, causing anomalies in composition of lymphoid cell fatty acids, which may explain the efficacy of elemental diets containing oils rich in n-6 polyunsaturates.     

Human adipose tissue cannabinoid receptor 1 gene expression is not related to fat cell function or adiponectin level

CONTEXT: The cannabinoid receptor 1 gene (CNR1) is implicated in adipocyte function. OBJECTIVE: We investigated human adipose tissue CNR1 mRNA in relation to obesity, clinical and metabolic variables, adipocyte function, and adiponectin (ADIPOQ) levels. METHODS: We assessed sc fat biopsies from 96 obese and nonobese subjects and omental fat biopsies from 82 obese and nonobese subjects. RESULTS: The sc and omental adipose CNR1 gene expression were similar in obese and nonobese subjects. No association between either sc or omental adipose CNR1 mRNA levels and body mass index, waist circumference, plasma levels of glucose and insulin, lipids, or blood pressure was found. The sc and omental maximal adrenergic lipolytic activation as well as lipolytic adrenoceptor sensitivity were not related to CNR1 gene expression. Lipogenesis in sc adipocytes also showed no association with CNR1 mRNA levels. Finally, no relation was found between adipose CNR1 gene expression and ADIPOQ mRNA, adipose tissue adiponectin secretion, or circulating adiponectin. CONCLUSION: We found no association of human adipose tissue CNR1 mRNA expression with measures of body fat, metabolic parameters, fat cell function, or ADIPOQ expression. These data do not suggest a major role of human adipose CNR1 in fat cell function or metabolic disease development.     

Selective mobilisation of fatty acids from human adipose tissue

Background: Adipose tissue is a storage organ for dietary fat. During fasting, fatty acids are released into serum as free fatty acids (FFA). Experimental studies indicate that fatty acids are selectively mobilised from adipose tissue into serum. The aim of this study was to investigate whether the composition of the serum FFA fraction reflects selective mobilisation in the fasting state in humans. Methods: The fatty acid composition of fasting serum FFA and adipose tissue were analysed from 112 patients with myocardial infarction and 107 healthy control subjects using gas-liquid chromatography. The subjects' habitual diet was analysed using a food-frequency questionnaire. Results: Significant correlations were found between serum FFA and adipose tissue, particularly for the percentage content of linoleic acid (r=0.73), eicosapentaenoic acid (r=0.68), alpha-linolenic acid (r=0.67) and palmitoleic acid (r=0.60). Percentage contents of palmitic, stearic, linoleic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acid were higher in serum FFA than in adipose tissue, whereas oleic and palmitoleic acid were relatively more abundant in adipose tissue. This may indicate that the former group of fatty acids is preferentially mobilised from adipose tissue into serum. High correlations for polyunsaturated fatty acids were observed between percentage contents of dietary and adipose tissue fatty acids. The correlation of fatty acids between diet and serum FFA was weak, but a tendency towards higher correlations for polyunsaturated fatty acids was observed. Conclusions: Our findings are compatible with the hypothesis that, in the fasting state, fatty acids are selectively mobilised from adipose tissue into serum FFA.     

Relationship of dietary fat and serum cholesterol ester and phospholipid fatty acids to markers of insulin resistance in men and women with a range of glucose tolerance

High-fat diets are associated with insulin resistance, however, this effect may vary depending on the type of fat consumed. The purpose of this study was to determine the relationship between intakes of specific dietary fatty acids (assessed by 3-day diet records and fatty acid composition of serum cholesterol esters [CEs] and phospholipids [PLs]) and glucose and insulin concentrations during an oral glucose tolerance test (OGTT). Nineteen men and 19 women completed the study. Nine subjects had type 2 diabetes or impaired glucose tolerance. Fasting insulin correlated with reported intakes of total fat (r = .50, P < .01), monounsaturated fat (r = .44, P < .01), and saturated fat (r = .49, P < .01), but not with trans fatty acid intake (r = .11, not significant [NS]). Fasting glucose also correlated with total (r = .39, P < .05) and monounsaturated fat intakes (r = .37, P < .05). In multivariate analysis, both total and saturated fat intake were strong single predictors of fasting insulin (R2 approximately .25), and a model combining dietary and anthropometric measures accounted for 47% of the variance in fasting insulin. Significant relationships were observed between fasting insulin and the serum CE enrichments of myristic (C14:0), palmitoleic (C16:1), and dihomo-gamma-linolenic (C20:3n-6) acids. In multivariate analysis, a model containing CE 14:0 and percent body fat explained 45% of the variance in fasting insulin, and C14:0 and age explained 30% of the variance in fasting glucose. PL C20:3n-6 explained 30% of the variance in fasting insulin, and a model including PL C18:1n-11 cis, C20:3n-6, age and body fat had an R2 of .58. In conclusion, self-reported intake of saturated and monounsaturated fats, but not trans fatty acids, are associated with markers of insulin resistance. Furthermore, enhancement of dihomo-gamma-linolenic and myristic acids in serum CE and PL, presumably markers for dietary intake, predicted insulin resistance.     

Adipose triglyceride lipase gene expression in human visceral obesity.

In comparison to subcutaneous (SC) fat, visceral adipose tissue is more sensitive to catecholamine-induced lipolysis and less sensitive to the antilipolytic effects of insulin. Variation in the expression of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) have been reported. We therefore hypothesized that expression of adipose triglyceride lipase (ATGL) is different in visceral and SC depot and investigated whether ATGL mRNA expression is related to obesity, fat distribution and insulin sensitivity. ATGL, LPL, and HSL mRNA expression was measured in 85 paired samples of omental and subcutaneous adipose tissue in normal glucose tolerant lean and obese individuals. In addition, we included a subgroup of obese (BMI >30 kg/m2) individuals with either impaired or preserved insulin sensitivity determined by euglycemic-hyperinsulinemic clamps. ATGL mRNA levels are significantly decreased in insulin resistant obese subjects. Independently of body fat mass, omental ATGL mRNA correlates with fasting insulin concentration, glucose uptake during the steady state of the clamp and HSL mRNA expression. In obese, but not in lean subjects, LPL and HSL mRNA expression was significantly higher in omental compared to SC fat. In both depots, HSL mRNA was significantly lower in obese individuals. Visceral HSL mRNA expression is closely related to adipocyte size and fasting plasma insulin concentrations, whereas visceral fat area significantly predicts visceral LPL mRNA expression. ATGL mRNA expression is not significantly different between omental and SC fat. HSL, but not ATGL mRNA expression is closely related to individual and regional differences in adipocyte size. Impaired insulin sensitivity was associated with decreased ATGL and HSL mRNA expression, independently of body fat mass and fat distribution.     

A diet high in fat stimulates adipocyte proliferation in older (22 month) rats

The effect of a high fat diet in stimulating adipocyte proliferation, as measured by the incorporation of [3H]-thymidine into fat cell DNA, was studied in 22-month-old female Sprague-Dawley rats. Rats were fed a low fat (n = 10) or a high fat diet (n = 9) for a total of six days. On days 4 and 5 of dietary manipulation, rats were injected with 80 microCi/100 g body weight of [3H]-thymidine. Rats were continued on their respective diets for one more day, starved for 72 h and then refed a stock diet for three weeks in order to increase turnover of stroma cells, thus diluting the specific activity of stromal DNA with minimal effect on specific activity of fat cell DNA. The diet groups did not differ significantly with respect to body masses, food intake, parametrial (PARA) and retroperitoneal (RP) depot masses, cell number or cell size. The specific activity of DNA in both PARA and RP depots was greater in the adipocyte than in the stromavascular fraction. Specific activity of fat cells was significantly greater from rats fed the high fat than the low fat diet in both PARA and RP depots. Radioautography of adipose tissue confirmed that there was a greater percentage of adipocyte nuclei labeled in the rats fed the high fat diet. Also, there were few labeled nuclei found in stroma cells. In conclusion, older female rats increased adipocyte proliferation when fed a high fat diet.     

Effects of systemic growth hormone (GH) administration on regional adipose tissue in children with non-GH-deficient short stature.

Chronic administration of exogenous GH to GH-deficient children is associated with a selective depletion of the abdominal sc fat depot and a resultant relative increase in gluteal, relative to abdominal, adipocyte lipid content. In GH-deficient children, the degree of this change in relative lipid content per adipocyte appears to be correlated with decreases in sensitivity of abdominal subcutaneous fat to the antilipolytic action of insulin. We studied abdominal and gluteal sc adipose tissue from 10 children with short stature (height less than 5% ile, growth velocity less than 5 cm/yr, bone age delayed at least 2 yr), who were not GH deficient based upon provocative testing (non-GH-deficient short stature) 1) before beginning and 2) after 3 months of therapy with exogenous GH (Humatrope, 0.1 mg/kg sc 3 times/week). In abdominal and gluteal adipocytes, we measured lipid content, rates of reesterification of fatty acids released by ongoing lipolysis and rates of in vitro lipolysis and lipogenesis in response to insulin, adenosine, and various adrenoreceptor agonists. These biochemical measures were correlated with measures of statural growth and adipose tissue distribution in each subject. We found that GH therapy was associated with a significant reduction in abdominal adipocyte size (0.48 microgram +/- 0.08 lipid per cell prior to therapy vs. 0.43 microgram +/- 0.08 lipid per cell after therapy, P less than 0.05) and a significant increase in responsiveness of gluteal sc adipose tissue to the lipogenic actions of insulin. The significant correlations of changes in abdominal adipocyte volume with changes in regional adipose tissue insulin sensitivity that were noted in GH-deficient children were not noted in this subject population, perhaps due to effects of endogenous GH on pretreatment insulin responsiveness of adipose tissue. These data reaffirm that GH has site-specific effects on regional adipose tissue depots.     

The effect of dietary fat content and composition on adipocyte lipids in normal and diabetic states

Cellular insulin resistance is a common feature of the diabetic and obese state. To determine the effect of dietary fat and the insulin resistant state of diabetes on adipose tissue composition, control and streptozotocin-induced diabetic rats were fed four diets differing in fat content (10 percent w/w or 20% w/w) and polyunsaturated to saturated fatty acid (P/S) ratios (0.2 or 2.0) for 6 weeks. At 3 weeks diabetes was induced in half the animals in each diet group. Increasing the fat content and P/S ratio of the diet increased the content of polyunsaturated fatty acids and decreased the contents of monounsaturated and omega-3 fatty acids. The higher level of C-18:2(6) and the lower levels of C20:4(6) and monounsaturated fatty acids observed in diabetic animals is consistent with altered desaturase enzyme activity. Diet and diabetes induced compositional changes in essential and non-essential fatty acids in the adipose tissue may alter the total body pools of available fatty acids for the synthesis of other lipids such as phospholipids.     

Differential effects of dietary saturated and trans-fatty acids on expression of genes associated with insulin sensitivity in rat adipose tissue

OBJECTIVE: Trans-fatty acids (TFAs) are formed during partial hydrogenation of vegetable oils and are shown to be more atherogenic than saturated fatty acids (SFAs). Our previous study showed that dietary TFAs decrease adipose tissue insulin sensitivity to a greater extent than SFAs in rats. We hypothesized that the effects of these fatty acids on insulin sensitivity could be mediated through an alteration in gene expression. In the current study we have investigated the effects of dietary TFAs or SFAs on expression of genes associated with insulin sensitivity in rat adipose tissue. DESIGN AND METHODS: Male weanling Wistar/NIN rats were divided into four groups and fed one of the following diets containing 10% fat (g/100 g diet) differing only in the fatty acid composition for 3 months: control diet (3.7% linoleic acid (LA)), SFA diet (5% SFA), TFA diet 1 (1.5% TFA + 1% LA) and TFA diet 2 (1.5% TFA + 2% LA). The mRNA expression of peroxisome proliferator-activated receptor gamma (PPARgamma), lipoprotein lipase (LPL), glucose transporter-4 (GLUT4), resistin and adiponectin was analyzed in epididymal fat using RT-PCR. The effects of TFA were studied at two levels of LA to understand the beneficial effects of LA over the effects of TFA. RESULTS: Both dietary SFA and TFA upregulated the mRNA levels of resistin. Dietary SFA downregulated adiponectin and GLUT4 and upregulated LPL, while TFA downregulated PPARgamma and LPL. The effects of dietary TFA on PPARgamma and resistin were not counteracted by increased LA (TFA diet 2). CONCLUSION: The effects of SFAs on the aforementioned genes except PPARgamma could be extrapolated towards decreased insulin sensitivity, while only the alteration in the mRNA levels of PPARgamma and resistin could be associated with insulin resistance in TFA-fed rats. These findings suggest that dietary SFAs and TFAs alter the expression of different genes associated with insulin sensitivity in adipose tissue.